Overview: This application seeks continued funding for the Washington University School of Medicine (WUSM) Nutrition Obesity Research Center (NORC). Since our NORC was first funded in 1999, it has served as a nidus for the growth and development of nutrition and obesity research at WUSM. The infrastructure provided by the NORC has created an environment that supports and stimulates cost-effective and high-quality research, collaborations between investigators, career development and training, and clinical activities in nutrition and obesity. Our NORC has a talented and diverse research base consisting of 109 investigators from 19 departments. These investigators have 179 nutrition/obesity-related grants, generating $42 million/year in direct costs. It is our intention o continue to grow nutrition and obesity-related activities, and to continue to bring state-of-the-ar basic and clinical research methods to NORC investigators. The overall research focus of the WUSM NORC has been: 1) Obesity: Pathophysiology, Complications and Therapeutics; 2) Nutrient Metabolism in Health and Disease; and 3) Growth, Development, and Aging. Newly emerging areas of major interest include: 4) Gut Microbiome and 5) Community Health. We propose an Administrative Core and 4 Biomedical Research Cores. The Clinical Science Research Core will provide assistance with: i) subject recruitment, design and performance of complex metabolic studies, ii) body composition assessments, iii) mixing of intravenous tracers and hormone solutions, iv) acquisition of tissue (adipose, muscle, intestine) samples, v) exercise (endurance and strength) and physical performance testing, vi) lifestyle (diet manipulation, weight loss and exercise) interventions, vii) ingestive behavior (taste perception and preference) testing, viii) cardiovascular assessments (e.g., echocardiography, endothelial function, carotid intima-media thickness); ix) measurement of stable isotope enrichment of metabolic substrates in blood and tissue samples, and x) mathematical modeling of tracer and non-tracer data to assess metabolic kinetics and -cell function. The Animal Model Research Core will provide services to investigators using murine models relevant to nutrition, including: i maintaining breeding colonies of genetically modified mice, ii) training in breeding and animal husbandry, iii) biochemical and molecular analyses of blood and tissue samples, iii) body composition analyses, iv) genotyping, and v) metabolic phenotyping. The Biomolecular Analyses Core will provide services to permit structural identification and quantitation of nutrition-related biomolecules in blood and tissue samples. The Adipocyte Biology and Molecular Nutrition Core will provide adipose tissue morphology, adipocyte and muscle cell lines for culture, gene and protein expression, mitochondrial physiology, and training in specialized research techniques. The collaborative and synergistic relationships among our NORC research base and our four Core laboratories will be formalized by promoting team science to further encourage interdisciplinary approaches to address important issues in nutrition and obesity. In addition, the NORC will fund 4 Pilot & Feasibility Awards/year to junior faculty and help mentor them.